Multiple organ infection and the pathogenesis of SARS

Gu, Jiang; Gong, Encong; Zhang, Bo; Zheng, Jie; Gao, Zifen; Zhong, Yanfeng; Zou, Wanzhong; Zhan, Jun; Wang, Shenglan; Xie, Zhigang; Zhuang, Hui; Wu, Bingquan; Zhong, Haohao; Shao, Hongquan; Fang, Weigang; Gao, Dongshia; Pei, Fei; Li, Xingwang; He, Zhongpin; Xu, Danzhen; Shi, Xeying; Anderson, Virginia M.; Leong, Anthony S.-Y.

In situ hybridization demonstrated SARS viral sequences in the cytoplasm of a large number of intact and degenerating epithelial cells of the lungs as well as in the scanty infiltrating lymphocytes and clustered macrophages ( Fig. 1, C and D) . Pulmonary epithelial cells were identified with immunostaining using antibodies to AE1 and AE3. The giant syncytial cells were particularly rich in hybridization signals. Monocytes and lymphocytes in blood vessels of the lungs also were positive for in situ hybridization ( Fig. 1 E) . Negative control for in situ hybridization of SARS genomic sequence of the lung showed no positive signal when an unrelated probe was used ( Fig. 1 F) . EM demonstrated SARS-like viral particles in the cytoplasm of the epithelial cells (Fig. 1 , H and I). In situ hybridization with specific probes, and colloid gold-labeled secondary antibodies detected specific positive signals in the cytoplasm of epithelial cell types I and II at the EM level ( Fig. 1 G) . Double labeling of SARS-infected cells with in situ hybridization and cytokeratin immunolabeling revealed that pulmonary epithelial cells were infected by SARS virus. The proliferative cells in the lungs were mainly type II cells as evidenced by their LM morphology.